Pain is a major symptom of many diseases, (e.g., cancer, arthritis, neurological diseases, heart attacks, etc.). Inadequate treatment of pain can lead to depression, anger, fear of disease progression and in some extreme cases, suicide.
Unfortunately, a patient's non-compliance or failure to take medication as prescribed, has been linked to inadequate treatment of pain. This is not surprising, since many pain treatment regimens involve administering pain medications by injection route (e.g., intravenous (IV), intramuscular (IM) or subcutaneous injection). The intravenous route is normally regarded as one of the most in-convenient routes to administer pain medication to achieve rapid pain relief. Intravenous administration may cause non-compliance, because not only do patients fear getting the injection, but unpleasant experiences such as pain, irritation and infection resulting at the injection site may also lead to non-compliance.
The intranasal route is currently receiving special interest, especially in the area of pain management. When medication is administered via the intranasal route, the medication is applied to the nasal mucosa where it is absorbed. The extensive network of blood capillaries under the nasal mucosa is particularly suited to provide rapid and effective systemic absorption of drugs. The intranasal route of administration should achieve similar dose to plasma concentration (bioavailability) and efficacy to that of the intravenous route.
Intranasal administration of medication provides numerous advantages over the intravenous route. The principal advantages of intranasal route are non-invasive delivery, rapid drug absorption, and convenience. The intravenous route, unlike the intranasal route, requires sterilization of hypodermic syringes and, in the institutional setting, leads to concerns among medical personnel about the risk of contracting disease if they are accidentally stuck by a contaminated needle. Strict requirements for the safe disposal of needles and syringes have also been imposed.
In contrast, intranasal administration requires little time on the part of the patient and attending medical personnel, and is far less burdensome on the institution than injectable routes. There is no significant risk of infection of the patient or medical personnel in the institutional setting when dealing with the intranasal delivery of medication.
A second important advantage of intranasal administration over intravenous is patient acceptance of the intranasal delivery route. In some cases, the injections cause burning edema, swelling, turgidity, hardness and soreness. In contrast, intranasal administration is perceived as non-invasive, is not accompanied by pain, has no after-effects and produces prompt relief in the patient exhibiting pain symptoms. This is of particular advantage when the patient is a child. Many, if not most, patients experience anxiety and exhibit symptoms of stress when faced with hypodermic injections via the IM or IV routes. Further, most people have some familiarity with nasal sprays in the form of over-the-counter decongestants for alleviating the symptoms of colds and allergies that they or a family member have used routinely. Another important consideration is that the patient can self-administer the prescribed dosage(s) of nasal spray without the need for trained medical personnel.
Among the many medications available to treat pain, opioids (e.g., morphine, methadone, hydromorphone, butorphanol, etc.) play one of the most important roles. The major advantage of the opioids is that they have an extensive history of use and are much more effective in treating severe pain than other classes of medications e.g. aspirin, acetaminophen, ibuprofen, etc. Another major advantage is that opioids exhibit few adverse effects on organs such as the stomach, liver, or kidney, other than very minor problems such as nausea or constipation. This is a major benefit over other medications such as aspirin or anti-inflammatory drugs that may cause ulcers, kidney problems, high blood pressure, or liver inflammation. In addition to relieving pain, opioids have other beneficial effects, such as, for example, peripheral arterial vasodilation, when treating heart attacks, provides the benefit of reducing oxygen demand on the heart.
There are different intranasal opioid formulations known in the pharmaceutical arts. However, some intranasal opioid formulations have reduced bioavailability at conventional doses. These formulations require more pain medication to be administered to the patient or else the pain will be inadequately treated.
Given the problems associated with inadequate treatment of pain and patient noncompliance, there is a need for intranasal opioid compositions that have improved bioavailability. There is also a need for intranasal compositions that improve patient compliance.